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@ARTICLE{Chan:167615,
      author       = {T. S. Y. Chan and D. Picard and C. E. Hawkins and M. Lu and
                      S. Pfister$^*$ and A. Korshunov$^*$ and M. F. Roussel and R.
                      J. Wechsler-Reya and J. Henkin and E. Bouffet and A. Huang},
      title        = {{T}hrombospondin-1 mimetics are promising novel
                      therapeutics for {MYC}-associated medulloblastoma.},
      journal      = {Neuro-oncology advances},
      volume       = {3},
      number       = {1},
      issn         = {2632-2498},
      address      = {Oxford},
      publisher    = {Oxford University Press},
      reportid     = {DKFZ-2021-00462},
      pages        = {vdab002},
      year         = {2021},
      abstract     = {Medulloblastoma (MB) comprises four subtypes of which group
                      3 MB are the most aggressive. Although overall survival for
                      MB has improved, the outcome of group 3 MB remains dismal.
                      C-MYC (MYC) amplification or MYC overexpression which
                      characterizes group 3 MB is a strong negative prognostic
                      factor and is frequently associated with metastases and
                      relapses. We previously reported that MYC expression alone
                      promotes highly aggressive MB phenotypes, in part via
                      repression of thrombospondin-1 (TSP-1), a potent tumor
                      suppressor.In this study, we examined the potential role of
                      TSP-1 and TSP-1 peptidomimetic ABT-898 in MYC-amplified
                      human MB cell lines and two distinct murine models of
                      MYC-driven group 3 MBs.We found that TSP-1 reconstitution
                      diminished metastases and prolonged survival in orthotopic
                      xenografts and promoted chemo- and radio-sensitivity via AKT
                      signaling. Furthermore, we demonstrate that ABT-898 can
                      recapitulate the effects of TSP-1 expression in MB cells in
                      vitro and specifically induced apoptosis in murine group 3
                      MB tumor cells.Our data underscore the importance of TSP-1
                      as a critical tumor suppressor in MB and highlight TSP-1
                      peptidomimetics as promising novel therapeutics for the most
                      lethal subtype of MB.},
      keywords     = {AKT (Other) / MYC (Other) / PI3K (Other) / TSP-1 (Other) /
                      medulloblastoma (Other)},
      cin          = {B062 / B300},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)B300-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33629064},
      pmc          = {pmc:PMC7890793},
      doi          = {10.1093/noajnl/vdab002},
      url          = {https://inrepo02.dkfz.de/record/167615},
}